Mutation spectrum of RB1 mutations in retinoblastoma cases from Singapore with implications for genetic management and counselling

• DOI: 10.1371/journal.pone.0178776
• Publication Date: 2017-06-02T17:50:40Z
• Authors: Swati Tomar; Raman Sethi; Gangadhara Sundar; Thuan Chong Quah; Boon Long Quah; Poh San Lai
• Keywords: Retinoblastoma; Penetrance; Proband

Retinoblastoma (RB) is a rare childhood malignant disorder caused by the biallelic inactivation of RB1 gene. Early diagnosis and identification carriers heritable mutations can improve disease outcome management. In this study, mutational analysis was conducted on fifty-nine matched tumor peripheral blood samples from 18 bilateral 41 unilateral unrelated RB cases combinatorial approach Multiplex Ligation-dependent Probe Amplification (MLPA) assay, deletion screening, direct sequencing, copy number gene dosage methylation assays. Screening both yielded mutation detection rate 94.9% (56/59) while only 42.4% (25/59) were detected if alone analyzed. Biallelic observed in 43/59 (72.9%) tumors screened. There 3 (5.1%) which no could be germline 19.5% (8/41) cases. A total 61 point identified, 10 novel. high incidence previously reported recurrent mutations, occurring at 38.98% (23/59) all Of interest three mosaic patients with retinoblastoma. Additionally, two to associated low-penetrance phenotypes: missense-c.1981C>T splice variant-c.607+1G>T, proband, respectively. These findings have implications for genetic counselling risk prediction affected families. This first published report spectrum Singapore shows that further improved screening strategies are required order provide definitive molecular every case RB. Our also underscore importance testing supporting individualized management plans asymptomatic family members carrying low-penetrance, mosaicism or phenotypes.